Our Peptide Chemistry team, in collaboration with scientists at Merck & Co., Inc., Rahway, NJ, USA, reported on the design, synthesis and characterization of potent and stable peptides able to inhibit the binding of NRF2-MAFG heterodimeric transcription factor to Antioxidant Response Element (ARE) DNA sequence. These peptides may provide interesting starting points for the development of therapeutic agents for tumors with a dysregulated NRF2-dependent pathway. Highly complex peptide heterodimers of long NRF2 and MAFG fragments exploiting various heterodimerization chemistries were generated based on a novel hybrid homology model. The model was built from the published crystal structure of the homodimeric MAFG/MAFG complex on DNA and the NMR structure of the NRF2 N-terminal loops of the DNA-binding domain. This type of strategy could prove useful to identify inhibitors of transcription factors beyond NRF2.